Bezuclastinib

胃肠道间质瘤的治疗领域，在2026年年初迎来了里程碑式的进展。一款全新的联合疗法经临床试验验证，让46%的晚期患者实现肿瘤显著缩小甚至完全消失，更将疾病进展或死亡风险降低50%。这是该领域20多年来首个突破性的二线治疗方案，为众多陷入治疗困境的患者带来了实实在在的生存希望。 胃肠道间质瘤是一种起源于胃肠道间叶组织的恶性肿瘤，虽然发病率不如胃癌、肠癌普遍，但我国人口基数大，每年仍有2-3万人确诊。这种肿瘤的隐蔽性极强，早期几乎没有特异性症状，多数患者发现时就已是晚期，肿瘤出现转移或侵犯周围脏器，治疗难度大幅提升。 对于早期胃肠道间质瘤患者，手术切除是主要的治疗方式，术后5年生存率能达到50%-65%。但晚期患者的情况就糟糕得多，手术无法彻底清除肿瘤，术后复发率极高。即便接受了根治性手术，也有一半患者会在两年内复发，且复发后再切除仍大概率会再次复发，这成为患者和医生共同面对的难题。 靶向药物的出现，曾让晚期胃肠道间质瘤患者看到曙光。伊马替尼作为首款针对这类肿瘤的靶向药，能有效抑制肿瘤细胞增殖，显著延长患者生存期。但临床数据显示，约50%的患者在用药2-3年后会出现耐药性，肿瘤再次开始进展，后续的二线、三线靶向药疗效逐渐递减，治疗陷入瓶颈。 伊马替尼耐药后的治疗空白，是长期困扰临床的难题。众多晚期患者在一线药物失效后，面临着无药可用的尴尬处境，只能看着病情不断发展，生活质量也因药物副作用持续下降。医学界一直在寻找新的治疗方向，试图打破这一僵局，而新型联合疗法的出现，终于填补了这一临床空白。 这款引发广泛关注的联合疗法，由Bezuclastinib和舒尼替尼两款药物组成，二者各司其职、协同作战，形成了1+1＞2的治疗效果。2026年1月，美国FDA正式受理了该联合疗法的新药申请，还将其纳入实时肿瘤审评项目，加速审批流程，足见其临床价值得到了高度认可。 Bezuclastinib是新一代选择性酪氨酸激酶抑制剂，它就像一把精准的“钥匙”，能精准锁定并抑制KIT D816V突变以及KIT外显子17的其他突变。这些突变在伊马替尼耐药的胃肠道间质瘤中十分常见，肿瘤的生长高度依赖于异常激活的KIT信号通路，这款药物正是从根源上阻断了肿瘤的增殖路径。 而舒尼替尼是一款临床应用已经成熟的多靶点酪氨酸激酶抑制剂，能同时作用于多个和肿瘤生长、血管生成相关的靶点，抑制肿瘤的营养供给。将它与Bezuclastinib搭配，既能精准打击肿瘤的特定突变，又能全面抑制肿瘤的生长和扩散，两种作用机制互补，让治疗效果实现了质的飞跃。 这款联合疗法的疗效，并非空口无凭，而是来自一项名为PEAK的3期临床试验，临床试验注册号为NCT05208047。该试验是全球范围内的随机对照研究，专门针对既往接受过伊马替尼治疗后疾病进展或无法耐受的胃肠道间质瘤患者，试验设计严谨，数据结果具备极高的参考价值。 此次临床试验的研究对象，都是临床中治疗难度极高的患者群体，他们大多处于局部晚期、转移性或不可切除的阶段，仅能耐受系统性治疗。试验将患者分为两组，一组采用Bezuclastinib联合舒尼替尼的治疗方案，另一组使用舒尼替尼单药治疗，通过对比来验证联合疗法的实际疗效。 联合治疗组采用的是每日口服Bezuclastinib，同时搭配37.5毫克舒尼替尼持续给药的方案，这一用药方式经过了反复的临床探索，兼顾疗效和患者的服药便利性。2025年11月，该临床试验的最新结果正式公布，一系列数据让医学界为之振奋，也让患者看到了新的希望。 在核心疗效指标无进展生存期上，联合疗法展现出了压倒性的优势。联合治疗组患者的中位无进展生存期达到16.5个月，也就是说一半的患者在接受治疗后，16.5个月内病情都没有出现任何恶化，而舒尼替尼单药治疗组的这一数据仅为9.2个月，差距十分明显。 更值得关注的是客观缓解率，这是衡量肿瘤缩小效果的关键指标。联合疗法组有46%的患者实现了客观缓解，也就是肿瘤达到显著缩小甚至完全消失的状态，而单药治疗组的客观缓解率仅为26%，联合疗法的效果提升了近一倍，这在晚期肿瘤治疗中是十分亮眼的成绩。 除了疗效显著，这款联合疗法还将患者的疾病进展或死亡风险直接降低了50%，这一降幅在胃肠道间质瘤的治疗中堪称突破性成果。截至2025年11月试验数据公布时，总生存期的数据尚未完全成熟，这也意味着大部分接受联合治疗的患者仍然存活，后续的疗效数据还有望继续刷新，带来更多惊喜。 一款好的治疗方案，不仅要疗效出众，安全性也必须有保障。这款联合疗法在临床试验中的安全性表现，同样让人放心。整体来看，联合疗法的耐受性良好，没有出现此前未被发现的新安全风险，其不良反应特征和舒尼替尼已知的安全属性基本一致，临床可控性强。 临床试验中观察到的3级及以上严重不良反应，主要包括高血压、中性粒细胞减少、转氨酶升高、贫血和腹泻，这些不良反应在联合治疗组和单药组的发生率相对接近。其中高血压在联合组和单药组的发生率分别为29.4%和27.4%，中性粒细胞减少的发生率均在15%左右，无明显差异。 在因治疗相关不良反应停药的比例上，联合治疗组为7.4%，单药组为3.8%，联合组虽略高，但整体仍处于较低水平。这说明绝大多数患者都能耐受这一联合治疗方案，不会因为严重的副作用而被迫中断治疗，能保证治疗的连续性和完整性。 FDA将该联合疗法纳入实时肿瘤审评项目，这一举措有着重要的意义。该项目允许药企在完整提交新药申请前，提前递交部分材料，让FDA提前启动审查，能大幅缩短审评周期，让安全有效的治疗方案更快地从临床试验走向临床应用，惠及更多急需的患者。 研发该联合疗法的Cogent Biosciences公司表示，会立即启动实时肿瘤审评流程，并计划在2026年4月完成全部申请材料的提交。公司负责人称，这一里程碑事件，充分认可了伊马替尼耐药胃肠道间质瘤患者的重大未满足医疗需求，也印证了这款联合疗法的临床价值。 更让人期待的是，这款联合疗法的探索之路并未止步于二线治疗。研发公司计划在2026年年中启动一项2期临床试验，探索该联合方案作为一线治疗，在携带特定突变的胃肠道间质瘤患者中的潜在获益。未来这款疗法有望覆盖更多患者群体，让更多人从中受益。 从临床试验的数据来看，接受这款联合疗法治疗的患者，平均治疗持续时间已经超过19个月，且疗效还在持续观察中。这意味着该疗法不仅能实现短期的肿瘤缩小效果，还能为患者带来长期的病情控制，让晚期患者实现高质量的带瘤生存成为可能。 此次联合疗法的突破，不仅仅是一款新药的即将上市，更代表着胃肠道间质瘤的治疗格局即将被改写。过去20多年，该领域的二线治疗一直没有新的获批方案，而这款联合疗法有望成为首个，为后续的药物研发和治疗方案探索提供了新的思路和方向。 对于广大胃肠道间质瘤患者而言，这一消息更是重燃了他们的生存信心。尤其是那些经历了伊马替尼耐药，在治疗道路上屡屡碰壁的晚期患者，终于有了新的治疗选择。随着新药申请的推进，这款联合疗法有望在不久的将来落地临床，让患者们早日用上这款突破性的治疗方案。 医学的进步，从来都是为了让更多患者摆脱病痛折磨。胃肠道间质瘤治疗的这一20年新突破，是无数科研人员和临床医生不懈努力的结果，也印证了精准医疗在肿瘤治疗领域的巨大潜力。未来，随着更多临床试验的开展和研究的深入，相信会有更多的治疗方案出现，为肿瘤患者带来更多希望。 从最初的手术治疗，到靶向药物的应用，再到如今联合疗法的突破，胃肠道间质瘤的治疗一直在不断前进。每一次进步，都意味着更多患者能获得更长的生存期、更好的生活质量。而这一突破也给其他肿瘤的治疗提供了借鉴，精准联合治疗或将成为未来肿瘤治疗的重要方向。 这款联合疗法的出现，让我们看到了医学攻克肿瘤的坚定步伐。46%的客观缓解率、50%的疾病进展风险降低、16.5个月的中位无进展生存期，一个个真实的数据，背后是无数患者的新生希望。我们期待这款疗法能尽快完成审批，早日走进临床，为更多胃肠道间质瘤患者带去福音。 医疗技术的发展永无止境，面对复杂的肿瘤疾病，医学界始终在迎难而上。胃肠道间质瘤治疗的这一突破，不是终点，而是新的起点。相信在精准医疗的不断发展下，未来会有更多的肿瘤被攻克，更多的患者能摆脱疾病的困扰，迎来健康的生活。 这款全新的联合疗法为胃肠道间质瘤患者带来了20年未有的治疗突破，46%的患者实现肿瘤缩小或消失的成绩，让整个医疗界都为之振奋。不知道大家身边是否有胃肠道间质瘤患者，对于这款即将上市的联合疗法，你有什么样的期待和看法，欢迎在评论区留言讨论。 免责声明：本文仅为科普知识分享，不构成任何医疗建议。文中涉及的研究成果、药物及疗法均处于临床研究或探索阶段，具体治疗方案需由专业医生根据患者个体情况制定。请勿仅凭本文内容自行判断病情或用药。

- Cogent will submit the PEAK New Drug Application (NDA) under previously announced RTOR designation; on track to complete NDA submission in April 2026 WALTHAM, Mass. and BOULDER, Colo., Jan. 26, 2026 (GLOBE NEWSWIRE) -- Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) for bezuclastinib in combination with sunitinib for patients with Gastrointestinal Stromal Tumors (GIST) who have received prior treatment with imatinib. “We are excited to announce this Breakthrough Therapy Designation which recognizes the potential for the bezuclastinib combination to substantially improve upon the currently available treatment options for patients with imatinib-resistant GIST,” said Andrew Robbins, Cogent’s President and Chief Executive Officer. “We look forward to the continued collaboration with the FDA as we work to bring the first new treatment option in over twenty years to this patient population.” This Breakthrough Therapy Designation is based on results from the PEAK trial which demonstrated a substantial and highly statistically significant clinical benefit on the primary endpoint of progression free survival (PFS), reducing risk of disease progression or death compared to the current standard of care by 50% (hazard ratio of 0.50, 95% CI: 0.39 – 0.65). mPFS, as assessed by blinded independent central review, was 16.5 months for the bezuclastinib combination vs. 9.2 months for sunitinib monotherapy. The combination was well tolerated, and no new safety risks were observed when compared to the known safety profile of sunitinib. Breakthrough Therapy Designation is intended to expedite the review of medicines that treat a serious or life-threatening condition and have shown clinical evidence indicating the potential for substantial improvement over available therapies. Earlier this month, the FDA agreed to accept Cogent’s NDA under the FDA’s Real-Time Oncology Review (RTOR) program which allows an applicant to pre-submit components of its NDA to allow the FDA to review clinical trial data before the complete filing is submitted and aims to provide a more efficient review process to ensure safe and effective treatments are available to patients as early as possible. Cogent plans to present full results from the PEAK trial at a major medical meeting during the first half of 2026. Additionally, in mid-2026 Cogent expects to initiate a Phase 2 trial investigating the benefit of the bezuclastinib plus sunitinib combination for first-line GIST patients with exon 9 mutations who are naive to, or recently initiated treatment with, imatinib. About Cogent Biosciences, Inc.Cogent Biosciences is a biotechnology company focused on developing precision therapies for genetically defined diseases. The most advanced clinical program, bezuclastinib, is a selective tyrosine kinase inhibitor that is designed to potently inhibit the KIT D816V mutation as well as other mutations in KIT exon 17. KIT D816V is responsible for driving systemic mastocytosis, a serious disease caused by unchecked proliferation of mast cells. Exon 17 mutations are also found in patients with advanced gastrointestinal stromal tumors (GIST), a type of cancer with strong dependence on oncogenic KIT signaling. In addition to bezuclastinib, the Cogent Research Team is developing a portfolio of novel targeted therapies to help patients fighting serious, genetically driven diseases initially targeting mutations in FGFR2/3, ErbB2, PI3Kα, KRAS and JAK2. Cogent Biosciences is based in Waltham, MA and Boulder, CO. Visit our website for more information at www.cogentbio.com. Follow Cogent Biosciences on social media: X (formerly known as Twitter) and LinkedIn. Information that may be important to investors will be routinely posted on our website and X. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding: the company’s plans to submit its PEAK NDA under RTOR and to complete the NDA submission in April 2026; the potential for the bezuclastinib combination to substantially improve upon the currently available treatment options for patients with imatinib-resistant GIST; the anticipated benefits of FDA’s RTOR and Breakthrough Therapy Designation; plans to present the full results from the PEAK trial at a major medical meeting during the first half of 2026 and the expectation to initiate in mid-2026 a Phase 2 trial investigating the benefit of the bezuclastinib plus sunitinib combination for first-line GIST patients with exon 9 mutations who are naive to, or recently initiated treatment with, imatinib. The use of words such as, but not limited to, "anticipate," "believe," "continue," "could," "estimate," "expect," "intend," "may," "might," "plan," "potential," "predict," "project," "should," "target," "will," or "would" and similar words expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results, the rate of enrollment in our clinical trials and other future conditions. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. We may not actually achieve the forecasts or milestones disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Such forward-looking statements are subject to a number of material risks and uncertainties including but not limited to those set forth under the caption "Risk Factors" in Cogent's most recent Annual Report on Form 10-K and/or Quarterly Report on Form 10-Q filed with the SEC. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as result of new information, future events or otherwise, except as required by law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date hereof. Contact: Christi WaarichSenior Director, Investor Relationschristi.waarich@cogentbio.com617-830-1653